ArticleBiomaterials2025
Synthetic hydrogel substrate for human induced pluripotent stem cell definitive endoderm differentiation.
Article in Biomaterials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Application and prospect of zinc oxide nanoparticle-enhanced biomimetic hydrogels in articular cartilage repair.Biochemistry and biophysics reports · 2026Review
- Xeno-Free Peptide-Functionalized Hydrogels Support hiPSC Encapsulation andbioRxiv : the preprint server for biology · 2026Article
- Intelligent design and application of molecular recognition hydrogels in tissue engineering.Materials today. Bio · 2026Review
- Synthetic thermoresponsive scaffolds for the expansion and differentiation of human pluripotent stem cells into cardiomyocytes.RSC advances · 2025Article
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Authors and funding
6 authors.
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Abstract
Human induced pluripotent stem cells (hiPSCs) can give rise to multiple lineages derived from three germ layers, endoderm, mesoderm and ectoderm. Definitive endoderm (DE) cell types and tissues have great potential for regenerative medicine applications. Current hiPSC differentiation protocols focus on the addition of soluble factors; however, extracellular matrix properties are known to also play a role in dictating cell fate. Matrigel™ is the gold standard for DE differentiation, but this xenogeneic, poorly defined basement membrane extract limits the clinical translatability of DE-derived tissues. Here we present a fully defined PEG-based hydrogel substrate to support hiPSC-derived DE differentiation. We screened hydrogel formulations presenting different adhesive peptides and matrix stiffness. Our results demonstrate that presenting a short peptide, cyclic RGD, on the engineered PEG hydrogel supports the transition from undifferentiated hiPSCs to DE using a serum-free, commercially available kit. We show that increasing substrate stiffness (G' = 1.0-4.0 kPa) results in an increased linear response in DE differentiation efficiency. We also include a temporal analysis of the expression of integrin and syndecan receptors as the hiPSCs undergo specification towards DE lineage. Finally, we show that focal adhesion kinase activity regulates hiPSC growth and DE differentiation efficiency. Overall, we present a fully defined matrix as a synthetic alternative for Matrigel™ supporting DE differentiation.
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Registered trials
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